Quantifying the Effect of Applying the NCEP ATP III Criteria in a Managed Care Population Treated With Statin Therapy

OBJECTIVES: Revised treatment goals suggested by the third report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) represent a challenge to both physicians and the health care industry. We sought to quantify the impact of these changes in a large managed care population being treated with statin therapy. METHODS: Using data collected from a retrospective chart review of 1,962 managed care enrollees who received statin drug therapy between February 2001 and August 2001, we quantified the low-density lipoprotein cholesterol (LDL-C) goals and goal attainment of this population according to both the NCEP ATP II and ATP III criteria and further identified independent predictors of ATP III goal attainment using multivariable logistic regression modeling. RESULTS: Overall, 21.1% (n = 414) of statin patients moved to a more stringent LDL-C goal when ATP III criteria were applied over ATP II. Substituting ATP III criteria for ATP II criteria resulted in a 6.8% decrease in the percentage of participants who had their most recent LDL-C value below the suggested goal, from 59.8% under ATP II to 53.0% under ATP III. Persons with existing coronary heart disease, diabetes, obesity, and stroke or transient ischemic attack were all less likely to meet the suggested NCEP ATP III LDL-C goal. CONCLUSIONS: Taking into account the revised risk stratification of the ATP III guidelines and the lack of LDL-C goal attainment in patients currently taking statins, there will be an increase in the number of statin patients who require dose or agent adjustment, combination therapy, or compliance counseling to achieve their lower LDL-C goal.


O R I G I N A L R E S E A R C H
Quantifying the Effect of Applying the NCEP ATP III Criteria in a Managed Care Population Treated With Statin Therapy BRIAN J. QUILLIAM, PhD; H. ED PEREZ, PharmD; VICKIE ANDROS, PharmD; and PETER JONES, MD, FACP oronary heart disease (CHD) is the number one cause of death in males and females in the United States. 1 It is estimated that every 29 seconds, 1 American will suffer a coronary event, and about every minute, 1 will die from such an event. 1 The objective of the Framingham Heart Study (FHS), initiated in 1948 by the National Heart, Lung, and Blood Institute (NHLBI) was to identify the common factors that contributed to cardiovascular disease over a long period of time in a cohort of patients who were free of known cardiovascular disease at baseline. 2 The FHS has identified high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity as major cardiovascular risk factors and has established a direct association between elevated low-density lipoprotein cholesterol (LDL-C) and coronary artery disease. 3 The FHS and other observational studies have also provided evidence implicating low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels in atherosclerotic risk. 4,5 In 1985, the NHLBI created the National Cholesterol Education Program (NCEP), and the Adult Treatment Panel (ATP) of the NCEP released its first guidelines in 1988 with an evidence-based emphasis on primary prevention of CHD. 6 In 1993, the second set of guidelines was published (ATP II), with the focus on secondary prevention (preventing coronary events in patients with established CHD). 7 In 2001, the ATP published the preliminary report of its third set of guidelines, with a focus on better methods to identify high-risk primary prevention candidates, such as those with multiple CHD risk factors. 8 The final report of the third set of guidelines (ATP III) was published in December of 2002. 9 A major change from ATP II to ATP III criteria was the introduction of CHD risk equivalents, conditions that carry a >20% risk of having a major coronary event in the next 10 years. Among the risk equivalents suggested by ATP III criteria are diabetes, carotid artery disease, peripheral arterial disease, and abdominal aortic aneurysms. 9 Targeting of patients with multiple (≥2) risk factors results in a greater percentage of the population who are candidates for lipid-lowering measures, including lifestyle changes and possibly drug therapy. It has been estimated that 1 out of every 5 adults may need lipid-lowering drugs, 9 representing an increase from 15 million to 36 million adults between the lipid goals in ATP III versus ATP II criteria. 10 To our knowledge, this is the first study to quantify the percentage of patients shifted to lower LDL-C goals suggested by the introduction of ATP III criteria in a managed care population as well as the percentage of patients who are meeting their target ATP III LDL-C goals.

II Methods
We performed secondary data analysis on data originally collected from a quality improvement (QI) initiative designed to identify inefficiencies in the care and management of patients with hyperlipidemia on drug therapy. Patients eligible for study inclusion in the original QI initiative were identified from pharmacy claims databases of commercial members prescribed statin therapy in 4 managed care organizations (MCOs) located in the southeastern, north central, and northeastern United States. Since this QI initiative involved review of the medical chart in the physician' s office, the top 200 physicians based on volume of statin therapy use were identified and the patients randomly selected from among these 200 higher-volume prescribers. The target was random selection of approximately 500 patients in each MCO.
For the QI initiative, nurses with prior data abstraction experience who were trained in the use of standardized data abstraction methods collected the data from the patients' medical records using a standardized data collection form. Approximately 20 nurses were performing chart reviews among all sites from February through August 2001. The data collection form solicited information on patient demographics, clinical history (family history of heart disease and smoking history), comorbid disease states (coronary heart disease, diabetes, hypertension, ischemic stroke, obesity, transient ischemic attack [TIA], and peripheral vascular disease), drug therapies (hypertension and cholesterol-lowering agents), and results of clinical examinations (blood pressure readings) and laboratory tests (total cholesterol, LDL-C, HDL-C, and triglycerides) pertinent to the management of hyperlipidemia.
This research project compares the data collected as part of this retrospective chart review from 1,962 patients with guidelines set forth by the Second and Third Panels of the NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. We determined each patient' s risk status and corresponding LDL-C goal according to these guidelines by accounting for the presence of CHD, CHD risk factors, and the presence of CHD risk equivalents. 7,9 Table 1 summarizes risk factors and risk equivalents identified by each of these guidelines. Information on carotid artery disease was not abstracted in the original QI initiative; therefore, for the current analyses, we used chart documentation of ischemic stroke or TIA as a proxy for carotid artery disease. Likewise, information on abdominal aortic aneurysms was not abstracted during the initial QI chart review. For our analyses, we assumed that abdominal aortic aneurysm would be rare within this population and therefore would not unduly influence NCEP goal categorization. 11 In Table 1, we present the LDL-C goals recommended by NCEP ATP II and ATP III criteria based on the presence of CHD, CHD risk factors, and CHD risk equivalents. Using information abstracted from the chart as part of the QI initiative, we deter-mined an LDL-C goal for each patient according to both the NCEP ATP II and NCEP ATP III criteria. Patients' individual LDL-C goal attainment success was determined by comparing their most recent LDL-C value documented in the chart (within the 2 years prior to chart review) with their LDL-C goal as defined by their risk status according to both guidelines.
Lastly, we developed a logistic regression model to identify independent predictors of NCEP ATP III goal attainment among a subsample of the population with an LDL-C value documented in the 2 years prior to the date of chart review (n =1,647). We considered demographic and clinical characteristics of the population as potential variables for model inclusion. The odds ratios (OR) and 95% confidence intervals (CI) derived from the final model provide estimates of effect for each of the factors while controlling for the influence of the other factors included in the model.

Demographics
Of the 1,962 patient charts reviewed, 55.7% (n = 1,092) were males and 44.3% (n = 870) were females. The mean age was 59.7 years and median age was 59.2 years. Among the study sample, 916 of the 1,962 patients were at least aged 60 years, accounting for 46.7% of the study population (Table 2). Weight was recorded in the chart for more than 97% (n = 1,907) of the study population, yet height was only recorded in 58.8% (n = 1,154) of the patient charts reviewed. For women, the average height and weight in charts with this information recorded  was 5'4" and 179 pounds compared with 5'10" and 207.2 pounds for men. Using available information on height and weight, we calculated body mass index (BMI) for 58.2% (n = 1,142) of the population; the average BMI was 30.2 (30.8 for women and 29.8 for men). Race and ethnicity were not documented in the chart for more than 60% of study participants; therefore, further presentation of this information is not possible.

Documentation of Recent LDL Cholesterol Readings
Of the 1,962 patients included, 315 (16.1%) did not have an LDL-C value measured in the 2 years prior to chart review. Therefore, in these patients, we were unable to determine whether their LDL-C target was attained.

Cholesterol-Lowering Medication Use
At the time of chart review, 93% of the study population was documented as being treated with cholesterol-lowering medica-tion either alone or in combination. The most commonly prescribed monotherapy agents in this population were atorvastatin (n = 755, 38.5%), simvastatin (n = 494, 25.2%), and pravastatin (n = 225, 11.5%). Combination therapy (the use of a statin plus an additional cholesterol-lowering medication) was relatively rare and was documented in less than 2% of the study population.

NCEP CHD Risk Factors, Risk Equivalents, and Corresponding LDL-C Goals
The prevalence of NCEP ATP II and ATP III risk factors and ATP III risk equivalents is presented in Table 2. Further, both ATP II and ATP III guidelines recognize an HDL cholesterol level of >60 mg/dL as protective against CHD and counted as 1 negative risk factor. In this population, 23.5% had a recent HDL-C cholesterol reading (in the 2 years prior to chart review) above this cutpoint. According to ATP III criteria, there was a shift in the population to lower LDL-C goals ( Figure 1). Overall, 21.1% (n = 414) of the population moved to lower suggested LDL-C goals when switching from ATP II guidelines to ATP III guidelines.

Intermediate Outcomes-NCEP Goal Attainment
When discussing outcomes related to hyperlipidemia management, intermediate end points and final end points need to be considered. Attainment of NCEP goal is considered an intermediate end point, and prevention of a first or second coronary event is considered a final end point. For the purpose of this study, NCEP goal attainment was the primary outcome. According to NCEP ATP II criteria, 59.8% of the population met their suggested LDL-C goal, compared with 53.0% of the population using LDL-C goals as suggested by NCEP ATP III criteria. Thus, 6.8% of the population (n = 134) who would have met goal according to ATP II guidelines did not meet their new LDL-C goal according to NCEP ATP III guidelines.
As expected, the percentage of patients with goal attainment according to both NCEP ATP II and ATP III criteria was greater among those with the least intensive LDL-C goal of <160 mg/dL. Additional information on goal attainment is presented in Figure 1. Further, among the 607 persons not achieving goal according to NCEP ATP III criteria, 60.3% required <20% reduction from their most recent LDL-C value to attain the suggested LDL-C cholesterol goals (Figure 2).

Independent Predictors of NCEP Goal Attainment
Results of multivariable logistic regression modeling are presented in Table 3. Persons with existing CHD were 64% less likely to meet their suggested NCEP ATP III LDL-C goal compared with persons without existing CHD (OR = 0.36, 95% CI 0.28-0.45). Similarly, persons with diabetes, carotid artery disease (stroke and/or TIA), obesity, smoking, and those with a Framingham risk >20% were less likely to meet their suggested LDL-C goal according to ATP III criteria. Age and gender did

II Discussion
The care and management of patients with hyperlipidemia is an increasingly important aspect of the managed care industry. As suggested by the NCEP ATP III guidelines, more patients will be identified as high risk and need more intensive treatment to reach their suggested LDL-C goal in order to reduce cardiovascular events. 9 To our knowledge, this is the first study quantifying the differences in LDL-C goals required and the changes in goal attainment as suggested by NCEP ATP III criteria. Our findings suggest that an additional 6.8% of our managed care population taking statin therapy were not at the lower LDL-C goals: 24.1% under ATP II versus 30.9% under ATP III.
In this large population of managed care enrollees taking statin therapy, the prevalence of CHD, CHD risk factors, and CHD risk equivalents was considerable. More than 30% of the population had existing CHD, 24% had diabetes, and 60% had greater than 2 CHD risk factors. Based on the presence of these factors, approximately 21% of this cohort shifted to more stringent LDL-C goals when ATP III criteria were used rather than ATP II criteria. In addition, a greater percentage of these patients had a recent LDL-C reading that, while at or below their ATP II LDL-C goal, did not meet their suggested ATP III LDL-C goal.
In our sample, 59.8% of the population was at or below their ATP II LDL-C goal while 53.0% were at or below the ATP III LDL-C goal, a 6.8% decrease in goal attainment. Previous data published from the Lipid Treatment Assessment Project (L-TAP) indicated that only 38% of their overall study population, 37% of the high-risk patients (≥2 risk factors without CHD), and 18% of patients with existing CHD who were also on stable diet or lipid drug therapy were meeting their desired LDL-C goals according to NCEP ATP II criteria. 12 Although our estimates of persons meeting goal is higher than those published in the L-TAP study, the patients in our sample were all identified from a pharmacy claims dataset as being prescribed statin therapy. Despite treatment with statin therapy, the percentage of patients not meeting goal approximated 24% and 31% according to ATP II and III criteria, respectively. Other studies using less stringent criteria than those of NCEP ATP III have similarly shown that a large percentage of patients treated with drug therapy do not meet LDL-C goals. [13][14][15] Of the 596 persons (30%) with existing CHD included in our sample, only 38.1% were meeting LDL-C goals (<100 mg/dL) according to ATP III criteria, and 39.4% were meeting LDL-C goals according to ATP II criteria (≤100 mg/dL). Further, in multivariable logistic regression modeling, CHD was an independent predictor of nongoal attainment. Only 18% of persons with existing CHD in the L-TAP study were meeting their ATP II goal of ≤100 mg/dL. 12 In a randomized controlled trial with CHD patients who had "normal" total cholesterol, the authors showed that many needed combination drug therapy to reach desired LDL-C goals. 16 In a large claims analysis, Straka et al. demonstrated that only 23.3% of persons with existing CHD were meeting their LDL-C goal according to ATP II criteria. Also, the majority of CHD patients who were not meeting goal were already prescribed lipid-lowering therapy. 17  strategies to manage patients with existing CHD may include dose titration, switching to another statin, or the use of combination lipid drug therapy. In this study, the documented presence of risk factors for CHD was common. According to ATP II criteria, diabetes is a risk factor for CHD, while in ATP III, diabetes is a risk equivalent for CHD since the probability of a diabetic patient developing a major CHD event in the next 10 years is greater than 20%. 9 The high prevalence of diabetes in the U.S. population 18 identifies a new high-risk group requiring more intensive therapy to achieve LDL-C goals. In our sample, 289 of the 478 (60.5%) diabetic patients who did not have existing CHD fell in the lowest LDL-C goal of <100 mg/dL, as opposed to an LDL-C goal of either <130 mg/dL or <160 mg/dL, depending on the presence of other CHD risk factors in other ATP criteria. Among these diabetic patients without existing CHD who were identified as taking statin therapy, only 33% attained an LDL-C of <100 mg/dL. Straka and colleagues reported that 21% of their diabetic population without CHD attained an LDL goal of ≤100 mg/dL, although only 29% of those meeting goal were identified as taking cholesterol-lowering medication. 17 Other studies assessing the proportion of diabetic patients meeting NCEP ATP II goals also indicate a low goal attainment within this population. 11,17 While changes in other risk factors between ATP II to ATP III may have a smaller impact on the numbers of patients that need more intensive management, our data indicate that changing diabetes from a risk factor for CHD to a CHD risk equivalent is quite significant. As the size of the diabetic population continues to increase, a greater emphasis on primary CHD prevention within this population will become more important for MCOs.
During this chart review process, approximately 16% of the population did not have an LDL-C laboratory value documented in their chart, despite the fact that all patients were identified for inclusion in the QI initiative on the basis of receipt of at least 1 prescription for a statin drug. With an increase in the percentage of high-risk patients who need a lower LDL-C goal, it is disappointing that LDL-C is not being followed more closely by primary care physicians in an outpatient managed care setting. Greater educational efforts should focus not only on routine lipid screening but also on regular follow-up of lipid laboratory testing. Further, it is important to note that while we chose to collect data on LDL-C values in the 2-year period prior to chart review, we found that only 75% of our sample had an LDL-C reading documented within the 1 year prior to chart review.
While our population was already being treated with lipid drug therapy, there is undoubtedly a greater percentage of the untreated population who will need to be treated to meet NCEP ATP III goals. Both treatment and monitoring may increase costs to the health care industry; however, the increased cost savings in the prevention of major CHD events and revascularizations will potentially make such endeavors cost effective.
Despite the shifts to more aggressive LDL-C goals suggested by changes from ATP II to ATP III guidelines, the average additional percent reduction in LDL-C was 18.1% among the 607 participants not meeting goal according to ATP III criteria. More than 60% needed a reduction in their current LDL-C value (within the previous 2 years) by 20% or less to meet goal. Therefore, in those persons not meeting goal, additional treatment strategies could quite reasonably include more attention to lifestyle modification, increased counseling on medication compliance, dose titration or switching to another statin, and combining lipid-lowering drugs that are complementary in reducing LDL-C levels (e.g. statins and bile acid-binding resins). [19][20][21][22] Limitations Among the limitations of this study was our reliance on medical chart documentation to ascertain the presence of CHD, CHD risk factors, CHD risk equivalents, and LDL-C values. As part of the original QI initiative, trained nurses reviewed the medical  records of eligible patients in the office of the physician identified in the pharmacy claims data as the prescriber for statin drug therapy. Since several physicians may be involved in the care of any given patient, all the information of interest may not have been available in the particular prescriber' s office where the medical chart was reviewed. It is possible that some of the missing LDL-C values could have been recorded in the medical charts of other physicians who cared for these MCO patients.
Another important limitation is the lack of information regarding dose titration and patient compliance to their cholesterol-lowering medication regimen. Although the study population was identified for the original QI initiative from a pharmacy claims database, these original claims data were not available for the current research project. As part of the original QI project, trained nurses abstracted information on the patient' s current cholesterol-lowering drug regimen as documented in the chart at the time of chart review. A history of dose titration and information about switching between antilipid agents were not collected. Therefore, we did not measure compliance with treatment or adherence or persistence with drug therapy and did not record the number of days of statin drug therapy that were dispensed. However, since nearly 31% of the population was not meeting its NCEP ATP III goal, there is a clear opportunity to improve goal attainment through mechanisms such as increased emphasis on physician monitoring and management of these patients and increased patient compliance to improve goal attainment.
Lastly, the patients randomly selected in these analyses were identified in pharmacy claims data as receiving prescriptions for statin drug therapy. The high prevalence of hypertension, diabetes, obesity, and other comorbidities within this population suggests that patient selection on the basis of drug therapy captures a relatively more complex population compared with patients being managed with diet and other lifestyle modifications alone. Therefore, the results of this study may not be generalizable to the general population of patients with hyperlipidemia.

II Conclusion
The advent of the more rigorous NCEP ATP III guidelines will likely result in more patients on cholesterol medication requiring additional interventions-management to attain LDL-C goals. In this study of MCO patients receiving statin drug therapy (the most common treatment for hyperlipidemia), the percentage of patients achieving their LDL-C goal dropped by 6.8% from 59.8% under the criteria of ATP II to 53.0% under the criteria of ATP III. Conversely, the proportion of statin patients not at LDL-C goal rose from 24.1% under ATP II to 30.9% under ATP III criteria.